A Pilot Study of the Mechanism of Synergism Between FP and Salmeterol in Preventing COPD Exacerbations

NCT00116402 | Completed Phase 1 DMC

• 1 other identifier: 13426B
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the blood and airway of subjects with mild to moderate COPD while undergoing standard treatment.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

COPD; Chronic Obstructive; Pulmonary Disease; Inhaled Corticosteroids; Airway Inflammation; Bronchoscopy

Outcome Measures

Primary Outcomes (1)

• To evaluate blood and airway neutrophil population in COPD patients by examining adhesion and migration in patients with mild to moderate COPD

  12 weeks

Study Arms (2)

1

ACTIVE COMPARATOR

will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID

Drug: fluticasone and salmeterol

2

ACTIVE COMPARATOR

salmeterol 50 mcg BID then crossover to combination therapy with fluticasone 220 mcg BID

Drug: fluticasone and salmeterol

Interventions

fluticasone and salmeterol DRUG

1. will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID 2. will start with salmeterol 50 mcg BID first and then crossover to combination therapy with fluticasone 220 mcg BID.

1; 2

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females \> 50 years of age
• Physiologic evidence of COPD defined per ATS guidelines as: cigarette smoking history \>20 pack years, FEV1/FVC \<70%
• Patients must have a post-bronchodilator FEV1 \>50% of predicted value at enrollment
• Patient must have an O2 saturation measure by pulse oximetry \>90% on RA
• Must be able to participate in the study, willing to give informed consent, and comply with the study restrictions

You may not qualify if:

• Women of child-bearing potential defined as females who are less than 5 years post menopausal unless they have had a hysterectomy or bilateral oophorectomy
• Observation of any solitary nodule in the lung requiring further medical intervention
• Patients on maintenance therapy with oral steroids
• Patients with giant bullous disease
• Significant other medical conditions, which in the opinion of the investigator, will interfere with the patient's ability to perform the study tests
• Presence of a coagulopathy as defined by a platelet count \<100,000/mm3, and PT and PTT \>1.2 x the upper limit of normal
• Concurrent enrollment or participation in any other clinical trials within the past 30 days
• Primary diagnosis of asthma
• History of alpha 1 antitrypsin deficiency
• Any clinically significant and active pulmonary disease that could contribute to dyspnea
• Current systemic and inhaled steroids and theophylline

Sponsors & Collaborators

• University of Chicago: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Department of Medicine, Pulmonary & Critical Care Section, The University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (12)

• Soriano JB, Kiri VA, Pride NB, Vestbo J. Inhaled corticosteroids with/without long-acting beta-agonists reduce the risk of rehospitalization and death in COPD patients. Am J Respir Med. 2003;2(1):67-74. doi: 10.1007/BF03256640.

  PMID: 14720023 BACKGROUND

• Hanania NA, Darken P, Horstman D, Reisner C, Lee B, Davis S, Shah T. The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD. Chest. 2003 Sep;124(3):834-43. doi: 10.1378/chest.124.3.834.

  PMID: 12970006 BACKGROUND

• Hattotuwa KL, Gizycki MJ, Ansari TW, Jeffery PK, Barnes NC. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. Am J Respir Crit Care Med. 2002 Jun 15;165(12):1592-6. doi: 10.1164/rccm.2105025.

  PMID: 12070058 BACKGROUND

• Kim KP, Rafter JD, Bittova L, Han SK, Snitko Y, Munoz NM, Leff AR, Cho W. Mechanism of human group V phospholipase A2 (PLA2)-induced leukotriene biosynthesis in human neutrophils. A potential role of heparan sulfate binding in PLA2 internalization and degradation. J Biol Chem. 2001 Apr 6;276(14):11126-34. doi: 10.1074/jbc.M004604200. Epub 2000 Dec 15.

  PMID: 11118430 BACKGROUND

• Kim YJ, Kim KP, Han SK, Munoz NM, Zhu X, Sano H, Leff AR, Cho W. Group V phospholipase A2 induces leukotriene biosynthesis in human neutrophils through the activation of group IVA phospholipase A2. J Biol Chem. 2002 Sep 27;277(39):36479-88. doi: 10.1074/jbc.M205399200. Epub 2002 Jul 17.

  PMID: 12124392 BACKGROUND

• Chang PS, Absood A, Linderman JJ, Omann GM. Magnetic bead isolation of neutrophil plasma membranes and quantification of membrane-associated guanine nucleotide binding proteins. Anal Biochem. 2004 Feb 15;325(2):175-84. doi: 10.1016/j.ab.2003.10.039.

  PMID: 14751252 BACKGROUND

• Myou S, Zhu X, Boetticher E, Myo S, Meliton A, Lambertino A, Munoz NM, Leff AR. Blockade of focal clustering and active conformation in beta 2-integrin-mediated adhesion of eosinophils to intercellular adhesion molecule-1 caused by transduction of HIV TAT-dominant negative Ras. J Immunol. 2002 Sep 1;169(5):2670-6. doi: 10.4049/jimmunol.169.5.2670.

  PMID: 12193740 BACKGROUND

• Reumaux D, de Boer M, Meijer AB, Duthilleul P, Roos D. Expression of myeloperoxidase (MPO) by neutrophils is necessary for their activation by anti-neutrophil cytoplasm autoantibodies (ANCA) against MPO. J Leukoc Biol. 2003 Jun;73(6):841-9. doi: 10.1189/jlb.1102567.

  PMID: 12773517 BACKGROUND

• Zhu X, Munoz NM, Kim KP, Sano H, Cho W, Leff AR. Cytosolic phospholipase A2 activation is essential for beta 1 and beta 2 integrin-dependent adhesion of human eosinophils. J Immunol. 1999 Sep 15;163(6):3423-9.

  PMID: 10477614 BACKGROUND

• Meliton AY, Munoz NM, Liu J, Lambertino AT, Boetticher E, Myo S, Myou S, Zhu X, Johnson M, Leff AR. Blockade of LTC4 synthesis caused by additive inhibition of gIV-PLA2 phosphorylation: Effect of salmeterol and PDE4 inhibition in human eosinophils. J Allergy Clin Immunol. 2003 Aug;112(2):404-10. doi: 10.1067/mai.2003.1637.

  PMID: 12897749 BACKGROUND

• Reid DW, Ward C, Wang N, Zheng L, Bish R, Orsida B, Walters EH. Possible anti-inflammatory effect of salmeterol against interleukin-8 and neutrophil activation in asthma in vivo. Eur Respir J. 2003 Jun;21(6):994-9. doi: 10.1183/09031936.03.00109702.

  PMID: 12797494 BACKGROUND

• Qiu Y, Zhu J, Bandi V, Atmar RL, Hattotuwa K, Guntupalli KK, Jeffery PK. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003 Oct 15;168(8):968-75. doi: 10.1164/rccm.200208-794OC. Epub 2003 Jul 11.

  PMID: 12857718 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Lung Diseases

Interventions

Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fluticasone; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Imre Noth, M.D.

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2005
• First Posted: June 29, 2005
• Study Start: January 1, 2005
• Primary Completion: September 1, 2009
• Study Completion: October 1, 2009
• Last Updated: August 5, 2014

Record last verified: 2014-08

Locations

US (1)